A variety of 4-aminobutenols are known to have use themselves or as intermediates for the preparation of other chemical substances. For example, 4-dimethylamino-2-buten-1-ol could be used in the preparation of 4-dimethylaminobutyraldehyde diethyl acetal, an intermediate for a pharmaceutical compound, as disclosed in German Pat. No. 3,700,408.
3,4-Epoxy-1-butene (butadiene monoepoxide) is one potential substrate for the production of 4-aminobutenols. However, the reaction of nitrogen nucleophiles (e.g., amines) with 3,4-epoxy-1-butene typically yields a mixture of the 1,2 addition product (1,2 adduct) and the 2,1 addition product (2,1 adduct), and little or none of the 1,4 addition product (1,4 adduct). The reaction is illustrated below: ##STR1## See, e.g., M.G. Ettlinger, "Synthesis of the Natural Antithyroid Factor 1-5-Vinyl-2-Thiooxazolidone", 72 J. Amer. Chem. Soc. 4792-4795 (1950); U.S. Pat. No. 2,533,085 to Blicke; W.B. Wheatley, et al., "o-Benzylphenyl Derivatives. IV. beta-Chloro-ethylamines", 72 J. Amer. Chem. Soc. 1655-1659 (1950); M.P. Crozet and W. Kassar, "Synthesis and Radical Cyclization of Benzazepinoethane Thiols", 99 Compte Rendu Acad. Sci. Paris 99-101 (1985); U.S. Pat. No. 2,497,553 to Long, Jr.; A.A. Petrov and V.M. Albitskaya, "The Reaction of Divinyloxide with Amines", 26 Zhur. Obshchei Khim. 2125-2127 (1956); and F.F. Blicke and J.H. Biel, "Aminolysis Products of 1-Chloro-2-Hydroxy-3-butene, 1-Hydroxy-2-Chloro-3-butene and 1,2-Epoxy-3-butene", 79 J. Am. Chem. Soc'y 5508-12 (1957).
The regioselective addition of nitrogen nucleophiles to substrates to form 4-aminobutenols (the 1,4 adduct product) is extremely unpredictable in both result and yield. For example, in Tsuji, et al., "Regioselective 1,4 -Addition of Nucleophiles to 1,3-Diene Monoepoxides Catalyzed by Palladium Complex", 22 Tetrahedron Letters 2575-78 (1981) the formation of the 1,4 adduct from the palladium catalyzed reaction of 3,4-epoxy-1-dodecene and pyrrolidine is disclosed. Also, Trost, et al., "A Synthesis of Substituted Pyrrolidines via a Palladium(2+) Catalyzed Cyclization. An Unusual Approach to a Carbapenem", 108 J. Amer. Chem. Soc. 6053-54 (1986) discloses the formation of the 1,4 adduct from the addition of a nitrogen nucleophile to 3,4-epoxy-1-butene. On the other hand, Tsuda, et al., "Palladium(0)-Catalyzed (Reaction of Methyl-.gamma., .delta.-epoxy-sorbate with Nitrogen Nucleophiles", 54 Journal of Organic Chemistry 977-979 (1989) discloses that the palladium-catalyzed reaction of methyl-.gamma., .delta.-epoxysorbate with nitrogen nucleophiles is not regioselective for the 1,4 adduct.
It is widely recognized that the control of regiochemistry in the addition of nucleophiles to an intermediate unsymmetrical allyl-palladium substrate is an extremely complex problem. Many factors enter into the determination of which terminus of the electrophilic allyl ligand the nucleophile will preferentially attack. These factors include the steric nature of the nucleophile (see B.M. Trost, et al., "Allylic Alkylation: Nucleophilic Attack on pi-Allyl palladium Complexes", 100 J. Amer. Chem. Soc. 3416 (1978)) and the allyl substrate (see E. Keinen, et al. "Regioselectivity in Organo-transition-metal Chemistry. A Remarkable Steric Effect in pi-Allyl Palladium Chemistry", J. Chem. Soc., Chem. Commun., 648 (1984)); the electronic nature of the allyl substrate on the palladium (see J. Tsuji, et al., "Palladium-Catalyzed Regioselective Reactions of alpha-Acetoxy-beta, gamma,-Unsaturated Nitriles and gamma-Acetoxy-alpha, beta-Unsaturated Ester with Nucleophiles, "22 Tetrahedron Letters 2573 (1981)); the electronic nature of the other ligands on the palladium (see B. Akermark, et al., "Reactivity and syn-anti Isomerization of eta-3-geranyl and eta-3-neryl Palladium Complexes. Evidence for Electronic Control of the Regiochemistry of Nucleophilic Addition", 4 Organometallics 1275 (1985)); and the mechanism of the addition of the nucleophile (see Godleski, et al., "(pi-Allyl)Palladium Complexes of Norcamphene. Structure and Reactivity", 3 Organometallics 21 (1984)).
B. Trost and E. Keinan, "Steric Steering with Supported Palladium Catalysts", 100 J. Amer. Chem. Soc. at 7779 (1978) ("Keinan") discloses that using a polymer-bound catalyst may have some effect on the stereoselectivity of primary amine addition to cis-3-acetoxy-5-carbomethoxy-1-cyclohexene. However, the relationship of stereochemistry and regiochemistry is very complex and unpredictable. See, e.g., B.M. Trost, 4 Comprehensive Organic Synthesis 585-662 (1991) ("Trost") (discussing nucleophiles with allyl metal complexes). In addition, regiochemical control of the amination of allyl-palladium complexes is known to be particularly unpredictable. See, e.g., B. Akermark, et al., "Amination of pi-Allylpalladium Chloride Complexes. A Mechanistic Study", 103 J. Amer. Chem. Soc. 3037-3040 (1981).
Keinan also discloses that the use of a polymer-bound catalyst may have some effect on the regioselectivity of the addition of carbon nucleophiles to sorbyl acetate. However, amine nucleophiles often behave quite differently than carbon nucleophiles, as discussed in Trost. This fact, as well as the chemical disparity between sorbyl acetate and 3,4 epoxybutene, leave in doubt what effect a polymer-bound catalyst might have on the addition of amines to 3,4-epoxybutene.
Therefore, in light of the usefulness of 4-amino-substituted-2-buten-1-ols derived from 3,4-epoxy-1-butene and the inherent unpredictability of the result (relative to both the product and the yield) of attempted regioselective amine additions to 3,4-epoxy-1-butene, there continues to be a need for predictable, efficient synthetic processes for deriving 4-amino-substituted-2-buten-1-ols from 3,4-epoxy-1-butene. Even small relative increases in the yield of the 1,4 adduct from amine addition to 3,4-epoxy-1-butene can translate into large cost savings when the increase is extrapolated out to production scale.